Compensatory Prostaglandin E2 Biosynthesis in Cyclooxygenase 1 or 2 Null Cells

摘要: Prostaglandin E2 (PGE2) production in immortalized, nontransformed cells derived from wild-type, cyclooxygenase 1–deficient (COX-1−/−) or 2–deficient (COX-2−/−) mice was examined after treatment with interleukin (IL)-1β, tumor necrosis factor α, acidic fibroblast growth factor, and phorbol ester (phorbol myristate acetate). Compared their wild-type counterparts, COX-1−/− COX-2−/− exhibited substantially enhanced expression of the remaining functional COX gene. Furthermore, both basal IL-1–induced cytosolic phospholipase A2 (cPLA2), a key enzyme-regulating substrate mobilization for PGE2 biosynthesis, also more pronounced cells. Thus, have ability to coordinate upregulation alternate isozyme as well cPLA2 genes overcome defects prostaglandin biosynthetic machinery. The potential alter thereby compensate specific such has significant clinical implications given central role variety disease processes widespread use inhibitors therapeutic agents.